Capricor, Inc. is actively developing cardiac stem cell technologies for the treatment of heart disease. Capricor has exclusive license to a method to cultivate cardiac stem cells, present in small numbers in the adult human heart, in order to generate large numbers of cells with therapeutic value. This method is known as the cardiosphere method, and the cells derived have the ability to repair the injured heart, form new heart muscle, and create new blood vessels. These cells are currently being tested in a phase 1 clinical safety trial enrolling patients with a recent heart attack and resulting mild-to-moderate cardiac dysfunction. Cardiac biopsies are taken from patients using a minimally-invasive technique and cells are redelivered to the heart, following a period of cell expansion in the laboratory, using a catheter that inserts into the affected cardiac blood vessel. This project aims to first prepare for cell manufacturing in an FDA-compliant facility and to then test both the safety and efficacy of these cells in a sicker patient population using a more effective delivery method. The targeted patient group is those who have advanced heart failure (HF) and are receiving a ventricular assist device (VAD) as either a temporary measure while awaiting heart transplant or as a permanent medical solution. These patients face an annual mortality rate greater than 90% with standard therapy alone and stand to benefit greatly from a successful stem cell therapy. Preclinical data collected in a pig model demonstrates that directly injecting cells into the heart muscle is more effective than infusing them into a cardiac blood vessel. This delivery method is convenient to perform in HF patients at the time of surgical VAD placement. The patient's chest is open and cells can be injected using a typical syringe and needle. This study proposes to then follow patients in order to assess safety risks (including tumor formation, arrhythmias, toxic effects, and adverse clinical events) and efficacy measures (including the ability to wean a patient off of the VAD, heart function, viability of the heart muscle, and cardiac blood flow). This will be done in a phase 1 followed by a phase 2 series of clinical trials. This clinical trial series will take place at Cedars-Sinai Medical Center (CSMC). In order to prepare to conduct these clinical trials, manufacturing studies will first take place. Cell manufacturing protocols will be adapted such that they are compliant with cGMP (current Good Manufacturing Practices). Capricor will staff a preexisting facility and conduct a series of studies to validate the manufacturing process in that setting with full quality assurance and quality control oversight and measures in place. Capricor will then present the manufacturing plan, supporting preclinical data, and clinical protocol to the FDA for approval via the IND (Investigational New Drug) process while simultaneously seeking IRB (Institutional Review Board) approval from CSMC. Both approvals are necessary before the clinical trials can commence. Should the outcome of these trials prove positive, and the cell therapy safe and effective in VAD patients, Capricor will continue along the path to commercialize this cell product for use in this patient population. PUBLIC HEALTH RELEVANCE: Cardiovascular disease is the No. 1 cause of death in the United States. Cardiosphere-derived stem cells, isolated from a person's own heart using Capricor's patented technology, can alleviate and reverse many effects of the disease. The cardiosphere technology has the potential to affect many lives, to provide a possible cure for the disease or halt its progression, and to improve the health of the Nation.